FDA Grants Fast Track Designation to Nuvisertib for Myelofibrosis

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The FDA has granted fast track designation to the oral, investigational, highly selective PIM1 inhibitor nuvisertib (TP-3654) for the treatment of patients with intermediate- or high-risk myelofibrosis.1

Nuvisertib is being investigated in a phase 1/2 trial (NCT04176198) in patients with relapsed/refractory myelofibrosis.

"This positive momentum for nuvisertib signals strong promise in our pipeline and reflects our dedication to addressing unmet medical needs on behalf of patients with myelofibrosis and their families," Tsutomu Nakagawa, PhD, president and chief executive officer of Sumitomo Pharma America, stated in a news release. "Receiving FDA fast track designation for nuvisertib in the treatment of myelofibrosis reinforces our confidence in its potential as a treatment option for patients facing a poor prognosis with limited treatment options. We are committed to working closely with the FDA to progress the clinical development of nuvisertib and bring an alternative treatment option to patients with myelofibrosis."

Data from the phase 1/2 study presented at the 2025 EHA Congress showed that no dose-limiting toxicities (DLTs) were reported with nuvisertib monotherapy, and the agent was well tolerated.1,2

Additionally, 22.2% of patients experienced a spleen volume reduction of at least 25% (SVR25), and at least a 50% reduction in total symptom score (TSS50) was achieved by 44.4% of patients.1 Improvements in bone marrow fibrosis, hemoglobin, and platelet counts were reported in 42.9%, 24%, and 26.7% of patients, respectively.

Nuvisertib was also associated with significant cytokine modulation and an increase in increase of anti-inflammatory cytokines, which correlated spleen and symptom responses (P < .001) Notably, preclinical and clinical data support the evaluation of nuvisertib in combination with JAK inhibitors for this patient population.

The multicenter, open-label, dose-escalation trial is evaluating nuvisertib as monotherapy, as a ruxolitinib (Rituxan) add-on, and in combination with momelotinib (Ojjaara).3

For the monotherapy portion of the study, patients need to be at least 18 years of age with a confirmed pathological diagnosis of primary myelofibrosis, post–polycythemia vera myelofibrosis, post–essential thrombocythemia myelofibrosis, or intermediate- or high-risk primary or secondary myelofibrosis who were previously treated with a JAK inhibitor and were intolerant, resistant, refractory, or lost response to that agent. Those ineligible for a JAK inhibitor are also allowed to enroll. Other key inclusion criteria comprise an ECOG performance status of 0 or 1; a life expectancy of at least 6 months, and adequate renal, hepatic, and coagulation function. Splenomegaly is also required within 2 weeks of the first day of cycle 1.

In the ruxolitinib add-on arm, patients need to be on ruxolitinib for at least 6 months while receiving a stable dose of 5 mg to 25 mg twice per day for at least 8 weeks prior to the first dose of nuvisertib. Loss of response or suboptimal/plateaued response to ruxolitinib is required. In the momelotinib combination arm, prior treatment with a JAK inhibitor other than momelotinib is required.

The primary end points of the study are the incidence of DLTs, safety, and the proportion of patients to achieve a spleen volume reduction of at least 35%. Objective response rate, SVR25, TSS50, QT interval changes, and pharmacokinetics are secondary end points.

“The data observed to date demonstrate promising clinical activity for nuvisertib and the strong potential for selective PIM1 inhibition to slow the progression of myelofibrosis,” Jatin Shah, MD, chief medical officer of Oncology at Sumitomo Pharma America, added in the news release.1 "Patients with myelofibrosis are in need of new therapeutic approaches, including combination treatment options, that can provide increased and durable response rates with limited hematologic adverse events. The FDA fast track designation reinforces the potential of nuvisertib to provide clinical benefits for patients with myelofibrosis, an unmet medical need.”

References

1. Sumitomo Pharma America announces that nuvisertib (TP-3654) has received FDA fast track designation for the treatment of myelofibrosis. News release. Sumitomo Pharma America. June 12, 2025. Accessed June 13, 2025. https://news.us.sumitomo-pharma.com/2025-06-12-Sumitomo-Pharma-America-Announces-that-Nuvisertib-TP-3654-Has-Received-FDA-Fast-Track-Designation-for-the-Treatment-of-Myelofibrosis
2. Rein L, El Chaer F, Scandura JM, et al. Preliminary data from phase I/II study of nuvisertib, an oral investigational selective PIM1 inhibitor, showed clinical response correlating with cytokine modulation in patients with myelofibrosis. Presented at: 2025 EHA Congress; June 12-15, 2025; Milan, Italy. Abstract S221.
3. A study of oral nuvisertib (TP-3654) in patients with myelofibrosis. ClinicalTrials.gov. Updated June 4, 2025. Accessed June 13, 2025. https://clinicaltrials.gov/study/NCT04176198